Tardive dyskinesia is emerging as a significant neurological complication associated with long-term antipsychotic drug intake. The basic pathophysiology of this syndrome is unknown. Receptor alterations in the nigro-striatal pathways have been implicated and supported by some animal research. However, some earlier direct (CSF) measurements can be interpreted as suggesting pre-synaptic pathology. We propose a pilot project (small grant) to study CSF homovanillic acid following probenecid as a measure of central dopamine turnover in tardive dyskinesia, a procedure which should determine whether receptor hypersensitivity or persistent pre-synaptic excitation is the underlying lesion in this condition. Rational therapeutic approaches to tardive dyskinesia would be enhanced if this question could be answered.